Oral Nicotine Products for Nicotine Addiction

Overseen By John R Monterosso, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Southern California

Disqualifiers: Recent COVID-19, Cardiac event, Unstable psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different flavors and nicotine levels in oral nicotine products, such as gums and pouches, affect their appeal and potential for addiction. Researchers focus on whether these products might encourage dual use with electronic cigarettes, possibly leading to stronger nicotine dependence. Participants will try various nicotine gums and pouches to identify which combinations are most appealing and whether they increase addiction risk. Young adults aged 21-25 who exclusively use e-cigarettes and have not tried oral nicotine products before are ideal candidates for this study. As an unphased trial, this study allows participants to contribute to groundbreaking research on nicotine addiction.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does require that you are not using any other tobacco or nicotine products besides electronic cigarettes.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nicotine gum, used in this trial, is usually safe when used correctly. Some people might experience mild side effects like headaches, hiccups, or an upset stomach. Nicotine can be addictive, even in gum form, but the risk of dependence is low if directions are followed.

For nicotine pouches, studies suggest they pose fewer cancer risks compared to smoking regular cigarettes. However, they remain addictive, and the long-term health effects are not fully known. Stronger nicotine pouches may lead to more intense side effects and a higher risk of addiction.

Both nicotine gum and pouches are not recommended for young people or pregnant women, as nicotine can harm developing brains and overall health. Always use these products as directed to minimize risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these oral nicotine products because they offer a flexible and potentially more appealing alternative to traditional nicotine replacement therapies like patches and lozenges. Unlike conventional methods, these products come in various forms, such as gums and pouches, and offer different nicotine strengths, giving users more personalized options to manage their cravings. The gum and pouch formats can be more discreet and convenient, making it easier for people to integrate them into their daily routines. This adaptability and convenience could enhance user satisfaction and adherence, potentially leading to better outcomes in overcoming nicotine addiction.

What evidence suggests that this trial's oral nicotine products could be effective for nicotine addiction?

This trial will compare different oral nicotine products for nicotine addiction. Participants may receive low nicotine gum, which studies have shown can help people quit smoking, with success rates reaching up to 29% for some users. Another group will receive high nicotine gum, which provides quicker and longer-lasting relief from cravings compared to lower doses. Additionally, some participants will use low nicotine pouches, which research suggests might help people smoke less, though some users find them less satisfying than cigarettes. Lastly, high nicotine pouches are another option in this trial; they can help reduce smoking, but there is concern about potential addiction due to their high nicotine content. Overall, both gums and pouches show promise in reducing smoking, but effectiveness can vary based on dose and individual preferences. ^{6 7 8 9 10}

Who Is on the Research Team?

John R Monterosso, PhD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for young adult electronic cigarette users aged 21-25, with a focus on including sexual and gender minority participants. It's designed to understand how flavor (mint vs fruit) and nicotine strength (2mg vs 4mg) in oral nicotine products affect their appeal and potential for abuse.

Inclusion Criteria

I am willing to try the study's oral nanoparticle drugs.

I am between 21 and 25 years old.

I have never used any opioid narcotics.

Exclusion Criteria

Recent COVID-19+ (positive test in the past 30 days)

I was hospitalized for COVID-19 in the last 3 months.

Currently pregnant (based on urine pregnancy test), planning to become pregnant, or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (virtual)

Orientation

Participants complete an orientation session to provide informed consent and confirm eligibility

1 week

1 visit (virtual)

Sensory Appeal Session

Participants rate the appeal and sensory attributes of different ONPs after self-administration

1 day

1 visit (virtual)

Abuse Liability Sessions

Participants undergo two sessions to assess abuse liability of ONPs, including self-administration and monitoring

2 weeks

2 visits (virtual)

Follow-up

Participants are monitored for naturalistic use of ONPs and dual use liability

7 days after each abuse liability session

Daily electronic surveys

What Are the Treatments Tested in This Trial?

Interventions

• Oral Nicotine Products

Trial Overview The study examines the impact of different flavors and nicotine concentrations in gum and pouch oral nicotine products on their attractiveness and risk of misuse. Participants will rate these factors during virtual sessions, which could inform future regulations.

How Is the Trial Designed?

Group I: Low Nicotine Gum Active Control 2 Interventions

Participants in this arm will only use Lucy brand 2mg nicotine gum

Group II: High Nicotine Pouch Active Control 2 Interventions

Participants in this arm will only use ON! brand 6mg nicotine pouches

Group III: High Nicotine Gum Active Control 2 Interventions

Participants in this arm will only use Lucy brand 6mg nicotine gum

Group IV: Low Nicotine Pouch Active Control 2 Interventions

Participants in this arm will only use ON! brand 2mg nicotine pouches

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Among high school students in Southern California, non-tobacco oral nicotine products were used by 3.4% of students ever and 1.7% in the past 6 months, making them the second most prevalent nicotine product after e-cigarettes.

The use of non-tobacco oral nicotine products was notably higher among Hispanic students, sexual and gender minorities, and those with a history of using other nicotine products, highlighting the need for targeted public health surveillance and interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adolescent Use of Flavored Non-Tobacco Oral Nicotine Products. Harlow, AF., Vogel, EA., Tackett, AP., et al.[2023]

ZYN nicotine pouches contain no nitrosamines or polycyclic aromatic hydrocarbons (PAHs), indicating a potentially lower risk profile compared to traditional tobacco products, which often contain harmful constituents.

The levels of harmful and potentially harmful constituents (HPHCs) in ZYN were found to be similar to those in nicotine replacement therapy (NRT) products, suggesting that ZYN may be a safer alternative for nicotine delivery compared to moist snuff, which had significantly higher levels of harmful compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). Back, S., Masser, AE., Rutqvist, LE., et al.[2023]

Tobacco companies are increasingly entering the pharmaceutical market by acquiring subsidiaries and marketing nicotine replacement therapies like Zonnic gum in convenience stores, which may blur the lines between tobacco and therapeutic products.

The production of tobacco products that mimic pharmaceutical nicotine replacements, such as tobacco chewing gum and nicotine pouches, raises concerns about regulation and the effectiveness of tobacco cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Product Marketing Blurs the Line Between Nicotine Replacement Therapy and Smokeless Tobacco Products. Kostygina, G., England, L., Ling, P.[2019]

In a study involving 63 smokers, both snus and Zonnic were preferred over nicotine gum, showing greater effectiveness in reducing smoking urges and causing fewer side effects.

Participants experienced significant reductions in smoking (33% for gum, 37% for snus, and 42% for Zonnic), indicating that snus and Zonnic could be promising alternatives for nicotine replacement therapy, warranting further research on their long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized crossover trial of the acceptability of snus, nicotine gum, and Zonnic therapy for smoking reduction in heavy smokers. Caldwell, B., Burgess, C., Crane, J.[2022]

Medicinal nicotine has significantly improved smoking cessation rates over the past 20 years, with various products like patches, gum, and inhalers available to help smokers quit.

Innovative nicotine delivery methods, such as high-dose patches and new forms like drinks and lollipops, are being developed to enhance cessation success and manage withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine delivery systems. Shiffman, S., Fant, RV., Buchhalter, AR., et al.[2015]

In a study of 30 adult smokers, the 4-mg nicotine pouch significantly reduced withdrawal cravings by 23 points within the first hour, outperforming nicotine gum and placebo, which showed reductions of 15 and 8 points, respectively.

Participants rated the nicotine pouch as more helpful and pleasant to use compared to gum, indicating a preference that could enhance its effectiveness as a smoking cessation aid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single-blind, randomized, crossover trial of the effects of a nicotine pouch on the relief of tobacco withdrawal symptoms and user satisfaction. Thornley, S., McRobbie, H., Lin, RB., et al.[2015]

The novel tobacco-free nicotine pouch, ZYN, delivers nicotine effectively, with the 6 mg and 8 mg doses providing similar or faster nicotine absorption compared to traditional smokeless products like General snus and Longhorn moist snuff.

ZYN products showed a higher extraction fraction of nicotine (50-59%) compared to General snus (32%) and Longhorn moist snuff (19%), indicating a more efficient delivery of nicotine without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Comparison of a Novel Non-tobacco-Based Nicotine Pouch (ZYN) With Conventional, Tobacco-Based Swedish Snus and American Moist Snuff. Lunell, E., Fagerström, K., Hughes, J., et al.[2021]

Participants in focus groups perceived oral nicotine pouches (ONPs) as having similar or lower risks compared to traditional cigarettes and smokeless tobacco, although they acknowledged potential gastrointestinal and cardiovascular risks.

ONPs were viewed as situational substitutes rather than complete replacements for cigarettes and smokeless tobacco, which could lead to increased overall nicotine use in certain populations, particularly in Appalachia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of oral nicotine pouches & their marketing among Ohio Appalachia smokers and smokeless tobacco users. Long, L., Alalwan, MA., Keller-Hamilton, B., et al.[2023]

A survey of 6,131 U.S. participants aged 13-40 revealed that 33% had ever used oral nicotine products, with higher usage rates among those aged 21-40 compared to those under 21.

Marketing significantly influences the likelihood of purchasing oral nicotine products, especially among younger users, who are more likely to buy products like Zyn pouches when they perceive marketing messages about appealing flavors and social comfort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use, marketing, and appeal of oral nicotine products among adolescents, young adults, and adults. Gaiha, SM., Lin, C., Lempert, LK., et al.[2023]

A study analyzing 653 Reddit posts about oral nicotine pouches revealed that users predominantly shared positive experiences and product information, indicating a favorable public perception of these tobacco-free products.

The discussions also highlighted a significant interest in quitting traditional nicotine products, with 12.7% of posts focused on using oral nicotine pouches as a cessation tool, suggesting potential for these pouches in harm reduction strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. Shao, Y., Zou, J., Xie, Z., et al.[2022]

Exclusive users of Velo nicotine pouches showed significantly lower levels of harmful biomarkers compared to smokers, including a 91% reduction in total NNAL and a 46% reduction in carbon monoxide levels, indicating a lower risk of smoking-related diseases.

Velo users had higher total nicotine equivalents than smokers, but overall exposure to tobacco toxicants was much lower, suggesting that Velo pouches may be a safer alternative for nicotine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of biomarkers of exposure and potential harm, and physiological and subjective health measures in exclusive users of nicotine pouches and current, former and never smokers. Azzopardi, D., Haswell, LE., Frosina, J., et al.[2023]

In a study of 371 participants, those who adhered to wearing the active nicotine patch for at least 20 of the first 21 days had over three times the odds of achieving smoking abstinence at 6 weeks compared to nonadherent users (53.2% vs 21.5%).

Adherence to the nicotine patch did not significantly affect the likelihood of experiencing adverse events, indicating that using the patch as directed is both effective and safe for improving smoking cessation outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between adherence to daily nicotine patch use and treatment efficacy: secondary analysis of a 10-week randomized, double-blind, placebo-controlled clinical trial simulating over-the-counter use in adult smokers. Shiffman, S., Sweeney, CT., Ferguson, SG., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6873734/

Effect of nicotine 6 mg gum on urges to smoke, a ... This study provides evidence that the 6 mg nicotine gum provided a greater reduction, faster and longer relief of urges to smoke than the 4 mg nicotine gum.

2. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/add.70193?af=R

Nicotine pouches and clinical outcomes related to smoking ... First, while a 2-week crossover study showed that NPs reduced the number of cigarettes smoked, this reduction was similar to that achieved with ...

3. researchgate.net researchgate.net/publication/337434329_Effect_of_nicotine_6_mg_gum_on_urges_to_smoke_a_randomized_clinical_trial

(PDF) Effect of nicotine 6 mg gum on urges to smoke, a ... Conclusion: This study provides evidence that the 6 mg nicotine gum provided a greater reduction, faster and longer relief of urges to smoke than the 4 mg ...

4. tobaccopreventioncessation.com tobaccopreventioncessation.com/The-effectiveness-of-nicotine-replacement-therapy-on-oral-smokeless-tobacco-cessation,208023,0,2.html

The effectiveness of nicotine replacement therapy on oral ... A previous systematic review found that nicotine patches or gum did not receive much evidence to help individuals abstain from using smokeless ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06506162

Abuse Liability and Appeal of Oral Nicotine Products Initial evidence (primarily product interest survey data) suggests young adult EC users and adolescents may have higher affinity for nicotine gum than pouches, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9451008/

Lucy—Novel Flavored Nicotine Gum, Lozenges, and ... Lucy's promotion of its products as safe alternatives to other forms of tobacco, its packaging that recalls innocuous chewing gum, and its use ...

7. actchealth.com actchealth.com/blogs/nicotine-gum-5-side-effects-to-be-cautious-of

5 Harmful Side Effects of Nicotine Gum | ACTC Blog 5 Severe Side Effects of Nicotine Gum · 1. Increase in Stomach Problems · 2. Sleep deprivation · 3. Premature hair loss · 4. Increased Oral Cancer Risk · 5. Gum ...

8. amazon.com amazon.com/Lucy-Nicotine-Count-Spearmint-Alternative/dp/B09XWY25HJ

LUCY™ Nicotine Gum 2mg, 100 Count, Mint Lucy Nicotine gum is a form of Nicotine Replacement Therapy (NRT) that can help increase the chances of quitting successfully.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2214750024001628

Beyond smoking: Risk assessment of nicotine in pouches This study aims to assess nicotine in pouches and potential risks for health damage. 31 samples of nicotine pouches were collected and analyzed.

10. uhhospitals.org uhhospitals.org/blog/articles/2023/10/is-nicotine-gum-dangerous

Is Nicotine Gum Harmful to Your Health? Lucchesi says that NRT products are highly safe and effective when used properly. Multiple studies have shown that using NRT nearly doubles a ...